Mycoses最新文献

Background: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency, predisposing to life-threatening invasive mould infection (IMI). While antifungal prophylaxis has improved outcomes, IMI remains the leading cause of mortality in CGD. This study aimed to evaluate the clinical and fungal epidemiology of IMI among CGD patients in Türkiye and explore diagnostic and treatment challenges.

Methods: Demographics, clinical characteristics, IMI episodes, diagnostic methods, and antifungal prophylaxis regimens of 72 CGD patients followed at the Division of Paediatric Immunology of Marmara, Cerrahpaşa and Çukurova University School of Medicine, Türkiye between 1991 and 2022 were analysed. IMI episodes were classified as proven, probable, or possible based on the European Organisation for Research and Treatment of Cancer/Mycoses Study Group criteria.

Results: Of the patients, 79.1% were male, and 52.8% had autosomal-recessive CGD (AR-CGD). Forty-two IMI episodes were detected in 39 (54.2%) patients, predominantly involving the lungs. Proven IMI accounted for 28.5% of episodes, with Aspergillus fumigatus as the most frequent pathogen. Patients with X-linked CGD experienced earlier IMI onset than AR-CGD (34.0 months (IQR: 18.0-65.5) versus 122.0 months (IQR: 40.25-240.0; p = 0.005)). Presentation with IMI led to the CGD diagnosis in 20 (51.3%) patients, while 19 (48.7%) developed IMI under itraconazole prophylaxis (median: 96.0 months, IQR: 48.0-153.0). Of 13 deaths (18.0%), 84.6% were associated with IMI.

Conclusions: Our study highlights the persistently high burden of IMI among CGD patients, despite antifungal prophylaxis. Challenges in diagnosis, including limited access to invasive biopsy and diagnostic modalities, and gaps in prophylactic monitoring, underscore the need for optimised management strategies.

Purpose: Biologic agents have become a key treatment option for moderate-to-severe plaque psoriasis; however, the associated risk of superficial fungal infections, such as Candida and dermatophytes infections, remains unclear. This study aims to systematically assess the impact of different biologic agents on these infection risks and to compare the differences between them.

Methods: Research questions and keywords were developed based on the Population, Intervention, Control and Outcome (PICO) framework. A systematic search of PubMed, EMBASE, the Cochrane Library and Web of Science was conducted for randomised controlled trials (RCTs) published up to December 2024, using the keywords 'psoriasis', 'biologics', 'anti-IL-17', 'anti-IL-12/23', 'anti-TNF', 'superficial fungal infections', 'dermatophyte infections', 'Candida' and 'onychomycosis'. Meta-analyses were performed using RevMan 5.4 and STATA 16.0 software.

Results: A total of 644 records were identified, with 29 articles included in the final analysis. Meta-analysis indicated that compared with placebo, interleukin-17 (IL-17) inhibitors notably raised the risk of Candida infections (OR = 2.39, 95% CI = 1.84-3.11, p < 0.00001), whereas tumour necrosis factor-alpha (TNF-α) inhibitors (OR = 1.75, 95% CI = 0.53-5.82, p = 0.36) and interleukin-12/23 (IL-12/23) inhibitors (OR = 1.11, 95% CI = 0.27-4.63, p = 0.88) showed no significant differences. Cross-comparison demonstrated that IL-17 inhibitors had a higher risk of Candida infection compared to TNF-α inhibitors (OR = 2.23, 95% CI = 1.08-4.57, p = 0.03) and IL-12/23 inhibitors (OR = 4.21, 95% CI = 2.71-6.55, p < 0.00001). For dermatophyte infections, the overall risk associated with biologic agents was increased (OR = 1.89, 95% CI = 1.19-3.01, p = 0.007), IL-17 inhibitors showed a higher risk compared to IL-12/23 inhibitors (OR = 2.70 95% CI = 1.29-5.63, p = 0.008). Overall, biologic agents significantly increased the risk of superficial fungal infections compared to placebo (OR = 2.10, 95% CI = 1.73-2.55, p < 0.00001).

Conclusion: Biologic agents, particularly IL-17 inhibitors, notably increase the risk of superficial fungal infections in psoriasis patients. In clinical practice, targeted monitoring protocols should be established, including regular follow-up to promptly detect superficial fungal infections and initiate antifungal treatment as necessary.

Trial registration: PROSPERO: CRD42025636705.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has been reported worldwide. However, studies in Japan are limited, and no study has evaluated the relationship between the incidence of CAPA and specialist involvement in its diagnosis.

Objectives: We aimed to obtain new epidemiological data on CAPA in Japan and evaluate the relationship between the incidence of CAPA and specialist involvement in its diagnosis.

Methods: A survey was conducted among chief physicians at 760 training hospitals with at least 100 beds and accredited by the Japanese Respiratory Society or the Japanese Association for Infectious Diseases. Critical patients with COVID-19 diagnosed with CAPA between 1 January 2020 and 31 August 2023 were analysed. A literature review was conducted to evaluate the correlations between the incidence of CAPA and galactomannan (GM) testing and positivity rates.

Results: Responses were obtained from 221 of the 760 hospitals (29.1%). The incidence of CAPA was 0.67% (69/10,276). Hospitals with patients with CAPA had significantly more pulmonologists and infectious disease specialists than those without patients with CAPA. A strong positive correlation was observed between the incidence of CAPA and the number of pulmonologists per critical patient with COVID-19 (r = 0.824, p < 0.001). The literature review showed that bronchoalveolar lavage fluid GM testing rate was a strong positive correlation with the incidence of CAPA (r = 0.527, p = 0.014).

Conclusions: For the diagnosis of CAPA, its recognition by specialists primarily involved in managing critical patients with COVID-19 seems essential.

Objective: Trichophyton mentagrophytes complex species mainly cause superficial infections, with a high global incidence and affecting the quality of life of patients. The taxonomic identification between closely related species within the T. mentagrophytes complex remains problematic, especially between T. mentagrophytes and T. interdigitale. This study aimed to elucidate the species boundaries within the T. mentagrophytes complex.

Methods: We performed a phylogenetic tree, principal component analysis and population structure analysis based on whole genome single-nucleotide polymorphism (SNP) data of 157 T. mentagrophytes complex strains. The mating types, phenotypic and physiological characteristics of different populations of strains were detected to delimit the species within the complex.

Results: The phylogenomic analysis showed that the 157 T. mentagrophytes complex strains were divided into five populations and clustered into three major clades, namely the T. tonsurans (population I), T. interdigitale (populations II, III and V) and T. mentagrophytes (population IV) clades. T. interdigitale population III was significantly different from T. interdigitale population II in terms of nucleotide diversity, mating types, types of clinical disease caused and keratinolytic ability but similar to those of T. mentagrophytes population IV.

Conclusions: T. tonsurans, T. interdigitale and T. mentagrophytes could be regarded as independent species and all strains were divided into five populations. The finding that T. interdigitale population III strains (T. mentagrophytes genotype Tm-II*) are reclassified as T. interdigitale based on whole-genome analysis is notable and clarifies previous confusion in clinical microbiology labs.

Candida infections represent a major component of invasive and non-invasive mycoses globally, including the countries in the Arabian Peninsula. In this review, we present epidemiological features and trends, clinical manifestations, species distribution, antifungal susceptibility, and outcomes available for candidemia and candiduria in six countries of the Gulf Cooperation Council (GCC) and Yemen, all located in the Arabian Peninsula. We discuss gaps in knowledge and provide recommendations for improving various aspects for better management of infections by these fungal pathogens. Candida species prevail, with Candida albicans being the most isolated organism, though its prevalence varies over time. The second most frequently isolated species varies from country to country within the region. Generally, invasive infections by non-albicans Candida species are increasing. Candidozyma auris, formerly known as Candida auris, is causing serious health risks in all GCC countries, including those with appropriate diagnostic capacity and awareness.

Background: Oral terbinafine (TBF) is the drug of choice for onychomycosis management. To treat and heal the rough and thick nail tissue affected by fungal agents, a high dose and plasma concentration of this drug is necessary. This, however, poses a life-threatening risk due to the cytotoxic side effects, drug-drug interactions, and adverse physical and chemical properties associated with oral medications.

Objectives: This study aimed to employ nanostructured lipid carriers (NLCs) in a gel formulation to avoid side effects and to increase the absorption of topical TBF.

Methods: Terbinafine-loaded nanostructured lipid carriers (TBF-NLCs) were developed and optimised using an ultrasonic probe technique, resulting in the formulation of TBF-NLCs as a 1% w/w carbopol gel after verifying the characteristics associated with NLCs. In vitro antifungal susceptibility test (AFST) was conducted on 85 prevalent fungal species associated with onychomycosis, as well as on strains isolated from trial participants, following the CLSI M38-A2 and M27-A3 guidelines. A total of 60 volunteers were enrolled in this clinical randomised, double-blind, placebo-controlled study, divided equally into three groups prescribed with TBF cream 1%, TBF-NLCs gel 1%, and a placebo.

Results: A monodisperse suspension of spherical nanoparticles was successfully produced, exhibiting a zeta potential of 18.4 ± 1.02 mV, a Z-average of 131.7 ± 5.32 nm, a PDI index of 0.280 ± 0.017, and an EE percentage of 83.51 ± 3.52, all without any cytotoxic effects. The severity index showed a reduction from 65% and 55% to 35% and 10% in the TBF cream 1% and TBF-NLCs groups, respectively. From a mycological perspective, no significant negative results were noted during the 6th and 8th weeks of TBF-NLC 1% gel application.

Conclusion: The application of TBF-NLCs gel 1% demonstrated a quicker clinical recovery without adverse side effects compared to TBF cream, thus highlighting the effective nature of NLCs.

Background: Trichophyton quinckeanum is a zoophilic dermatophyte causing mouse favus, that was only sporadically detected in Germany for decades. Since 2014, an increasing number of isolates have been found in central Germany, giving rise to dermatophyte skin infections and skin appendix infections like tinea capitis or even kerion Celsi.

Objectives: The goal of this study was to characterize the specific features of dermatophyte infections due to T. quinckeanum.

Methods: We collected the data of 550 isolates of T. quinckeanum from Germany between March 2014 and December 2024 in the laboratory in Mölbis, Germany, in order to identify specific features of the zoophilic dermatophyte infection.

Results: To our knowledge, we present the highest number of cases ever published. Infection rates show a yearly recurring increase in autumn and winter months, whereas infection rates in spring and summer months are typically low. The peak of infections in the current epidemic in central Germany was seen in 2021. Mainly children, teenagers and young adults are affected.

Conclusions: T. quinckeanum has now become a relevant pathogen in Germany and surrounding countries. Even though the current epidemic is in decline, it is to be expected that in the future, infection rates will again correlate with the cyclic mouse population numbers, as they are the main source of infection. Climate change may also play an important role for mouse populations. Transmission to humans typically occurs via an intermediate host like cats (and less likely dogs), which is why pet owners are most at risk.

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection with increasing prevalence and mortality worldwide. Coinfection with chronic pulmonary aspergillosis (CPA) is a significant complication of NTM-PD, often complicating treatment and resulting in poor prognosis.

Objective: In this multicentre, retrospective cohort study, we examined the epidemiology, comorbidities, risk factors for CPA coinfection and long-term prognosis of patients with NTM-PD infected with CPA in Japan.

Methods: Patients aged ≥ 18 years with newly diagnosed NTM-PD who visited 18 hospitals between 2010 and 2017 in Kyushu, Japan, were included. Medical records were reviewed for patient characteristics, mycobacterial species, laboratory data, radiological features, Aspergillus coinfection and all-cause mortality rates. Risk factors for CPA coinfection were analysed using multiple logistic regression, and survival analysis was performed before and after propensity score matching with risk factors.

Results: Among 1304 patients with NTM-PD, 45 (3.5%) were diagnosed with CPA, including 42 with chronic progressive pulmonary aspergillosis. The risk factors for CPA coinfection included male sex, chronic obstructive pulmonary disease, oral corticosteroid use and cavity formation. All-cause mortality was significantly higher in patients with NTM-PD with CPA than in those without CPA (log-rank test, p < 0.001; crude hazard ratio [HR], 3.98). Survival analysis after propensity score matching suggested CPA was an independent poor prognostic factor (log-rank test, p = 0.036; adjusted HR, 1.59).

Conclusion: CPA is an independent poor prognostic factor in patients with NTM-PD. Clinicians must consider CPA when treating patients with NTM-PD, particularly those with high-risk factors, to ensure timely diagnosis and management.

Background: Trichophyton mentagrophytes ITS genotype VII (TMVII) has recently been identified as a cause of genital infections, raising concerns about its potential as an emerging sexually transmitted pathogen. However, the epidemiology and clinical features of TMVII infection remain poorly understood.

Objectives: To systematically review published TMVII cases and characterise its demographic distribution, transmission patterns, clinical manifestations and treatment outcomes.

Methods: A comprehensive literature review was conducted, including all published molecularly confirmed TMVII cases. Data on demographics, infection sites, co-infections and treatments were extracted and analysed.

Results: A total of 124 TMVII cases from 10 studies were included. Among 60 cases with detailed clinical data, tinea genitalis (36.7%) and tinea faciei/barbae/capitis (51.7%) were the common infection types. TMVII infection predominantly affected men who have sex with men (64%), with high co-infection rates of HIV (29.6%) and gonorrhoea (42.6%). Most cases were reported in France (49%) and Germany (35%), suggesting possible local transmission. Oral terbinafine (250 mg/day for 4-8 weeks) achieved a 64.4% cure rate (38/59 courses), while limited data indicated itraconazole and griseofulvin were also effective. Fluconazole showed no therapeutic efficacy.

Conclusion: TMVII can be transmitted through sexual activities, particularly affecting MSM and individuals with concomitant STDs. Current evidence suggests that oral terbinafine is effective, meanwhile other antifungals need further observation. Increased focus is warranted on the clinical management and monitoring of TMVII infection.

Background: Invasive fungal diseases (IFD) pose significant challenges in paediatric oncology. Their management is complicated by limited paediatric-specific evidence, lack of standardised protocols and variability in resources across centres. This study assessed current practices and addressed the challenges in the prevention, diagnosis and treatment of IFDs in paediatric oncology centres across Germany, Austria and Switzerland.

Methods: A questionnaire was distributed to senior paediatric oncologists in 70 paediatric oncology centres across Germany, Austria and Switzerland, gathering data on centre infrastructure, infectious disease (ID) expertise, annual cumulative IFD incidence in 2023, diagnostic tools, antifungal prophylaxis, treatment and follow-up practices for IFD. Responses were analysed descriptively.

Results: Sixty-two centres responded, with a median of 56 (IQR 40-75) new oncological diagnoses per centre; 54.8% of centres managed allogeneic HCT patients. IFDs were reported in 88.7% of centres, with a median cumulative IFD incidence of 4.6% (IQR 3.0%-5.9%). No significant association was found between cumulative IFD incidence and the number of transplants, antifungal prophylaxis protocols and availability of ID consultation services. ID consultation was available in 58.1% of centres, with 24/7 support provided in 41.7% of these centres. Larger centres more frequently had paediatric ID specialists, ID consultation services and access to therapeutic drug monitoring.

Conclusions: The observed heterogeneity in mycology expertise and IFD management strategies across centres reflects the inherent complexity of IFDs and the diagnostic and therapeutic uncertainties amid limited evidence. Strengthening oncology-ID networks and implementing digital consultation platforms may promote high-quality, equitable care, particularly for those with fewer in-house resources.